Vasoconstrictor antiseptic



Patented Jan. 2, 1951 VAS'OCONSTRICTOR ANTISEPTIC Victor JP. .Seeberg, Berkeley, Calif., assignor to Cutter Laboratories, Berkeley, Calif., a corporation of California No Drawing. Application November 24,1947, Serial No. 787;.857

9 Claims.

This invention relates to vasoconstrictorantiseptics for the treatment of .head colds (spenoethmoiditis) and has for its object the provision of a rapidly disintegrable and soluble penicillin-ephedrine tablet capable of yielding a clear, isotonic solution having an acceptable and known penicillin potency, and a known ephedrine and hydrogen ion concentration. Although the advantages of penicillin-ephedrine solutions for use as vasoconstrictor-antiseptics have been recognized for some time, considerable difiiculty has been experienced in making such solutions readily available to the patient.

Since penicillin solutions are unstable at room temperature, once made up, they must be maintained under refrigeration, and at best can be so held only for a period of approximately one week.

To enable a'physician or hospital attendant or pharmacist to make up solutions of this character, pharmaceutical manufacturers have attempted to provide them with bottles containing predetermined small quantities of the penicillin and vasoconstrictor in powder form, which if held under refrigeration, retain their stability for about one year. To make up the required solution from these powders, it is necessary only to add a predetermined volume of a suitable diluent.

Currently, vasoconstrictor-antiseptic combinations are marketed in two separate bottles, one containing a quantity of penicillin salt powder, and the other containing a quantity of a solution of the vasoconstrictor, and which also serves as a solvent for the penicillin salt. Either of the above methods usually entails the use of several bottles for each patient, the cost of which obviously must be borne by the patient. This increased cost is appreciable, since for each treatment of four to five days there will be required: two bottles with moisture-proof closures, two filling operations, two sets of manufacturing control operations, and a large bulk for refrigerated storage in the pharmacy and for refrigerated storage in the home.

To obviate this expense and inconvenience, it is the object of this invention to provide a penicillin-ephedrine tablet of the character above described, containing a predetermined amount of available penicillin and ephedrine, a buffer, and a tablet disintegrator, any desired number of which can be ackaged in a single bottle. The pharmacist or the patient can then merely add one such tablet to an atomizer or a dropperbottle, and add half ounce of water, to quickly obtain a fresh clear solution of penicillin and ephedrine, the solution being of proper concentration with respect to each ingredient, and also being isotonic and buiiered to the pH of optimum penicillin stability.

To produce tablets in commercial quantities having these characteristics, the following formula in which the boric acid serves as a lubricant, the citric acid and sodium bicarbonate serve as a tablet disintegrator, and all three of these reagents serve as an isotonic buffer, has been found satisfactory:

Formula per tablet Ephedrine sulphate crystals -gm e015 Boric :acid powder gm .200 Citric .acid gm .030 Sodium bicarbonate gm 4-050 Soluble penicillin salt units 15,750

In place of citric acid, any non-toxic organic acid capable of being reduced to a dry powder without any water of crystallization, for example, tartaric acid, can be used. The penicillin salt used .can be in the form of calcium penicillin, sodium penicillin or potassium penicillin, although calcium penicillin is preferred in so far as current government standards are concerned.

All of these ingredients listed in the formula, with the exception of the penicillinsalt, are predried to constant weight at about 140 F. The ephedrine sulphate crystals are passed through a 40 mesh screen, the citric acid and sodium bicarbonate through a mesh screen, the boric acid through an mesh screen, and the calcium penicillin through a mesh screen. This having been done, 0.125 gram of the boric acid is mixed with the other ingredients, and the mix sifted several times through a 20 mesh screen. The screened mix is then precompressed into slugs on a tablet machine, and the resulting slugs are comminuted by grinding and passing them through a 20 mesh screen. Following this the remainder of the screened boric acid (0.075 gram) is mixed with precompressed and ground slugs and formed into five-sixteenth of an inch (T -g") diameter tablets of approximately 0.38 gram each.

It should be particularly noted that the boric acid, citric acid and sodium bicarbonate perform a double function. In combination, these three reagents provide the required isotonic and buffering action, and are used in such quantities that when a tablet is dissolved in a predetermined volume of diluent, the resulting solutions will have a hydrogen ion concentration of about 6.0. The boric acid also serves as a lubricant during the tableting process, this being essential, due to the fact that in the absence of a lubricant, the ephedrine sulphate adheres so strongly to the surfaces of the tableting machine that the operation of the machine for more than a stroke or two would be precluded. The citric acid and sodium bicarbonate in addition to serving as a buffer, combine upon contact with water to produce a carbon dioxide gas in suiiicient quantities to disintegrate the tablet rapidly. Furthermore, these reagents produce a clear penicillin-ephedrine solution, a factor which from the psychological standpoint of the patient, is of considerable importance.

I claim:

1. A comminuted mix suitable for forming penicillin-ephedrine salt tablets comprising: a penicillin salt; a water-soluble ephedrine salt; boric acid; a dry organic acid and sodium bicarbonate.

2. A comminuted mix suitable for forming penicillin-ephedrine salt tablets comprising: a penicillin salt; a water-soluble ephedrine salt; boric acid; a dry organic acid and sodium bicarbonate, said ingredients being mixed in such proportions that when a predetermined quantity of the mix is dissolved in a predetermined volume of water the resulting solution will have a hydrogen ion concentration of about 6.0.

3. A comminuted mix suitable for forming penicillin-ephedrine salt tablets comprising: a salt of penicillin selected'from the group consisting of calcium penicillin, sodium penicillin and potassium penicillin; ephedrine sulfate; boric acid; a dry organic acid selected from the group consisting of citric acid and tartaric acid; and sodium bicarbonate.

4. A comminuted mix suitable for forming penicillin-ephedrine salt tablets comprising: penicillin; ephedrine sulfate; boric acid; citric acid and sodium bicarbonate intimately mixed in' the ratio of 15,750 penicillin units; 0.075 gram of ephedrine sulphate; 0.200 gram of boric acid;

i 0.03 gram of citric acid and 0.05 gram of sodium bicarbonate.

5. A penicillin-ephedrine salt tablet comprising: penicillin; a water soluble ephedrine salt;

4 boric acid; a dry organic acid and sodium bicarbonate. W

6. A penicillin-ephedrine salt tablet comprising: a penicillin salt selected from the group consisting of calcium penicillin, sodium penicillin and potassium penicillin; a water soluble ephedrine salt; boric acid; a dry organic acid selected from the group consisting of citric acid and tartaric acid; and sodium bicarbonate.

7. A penicillin-ephedrine salt tablet comprising: calcium penicillin; ephedrine sulphate; boric acid; citric acid and sodium bicarbonate.

8. A penicillin-ephedrine salt tablet comprising: a penicillin salt selected from the group consisting of calcium penicillin, sodium penicillin and potassium penicillin, ephedrine sulphate; boric acid; citric acid; and sodium bicarbonate, said ingredients being mixed in the ratio of about 15,750 penicillin units; 0.075 gram of ephedrine sulphate; 0.200 gram of boric acid; 0.030 gram of citric acid and 0.050 gram of sodium bicarbonate.

9. A penicillin-ephedrine salt tablet comprising: calcium penicillin; ephedrine sulphate; boric acid; citric acid; and sodium bicarbonate in the ratio of about 15,750 penicillin units; 0.075 gram of ephedrine sulphate; 0.200 gram of boric acid; 0.03 gram of citric acid and 0.05 gram of sodium bicarbonate.

VICTOR P. SEEBERG.

REFERENCES CITED The following references are of record in the file of this patent: a

Wood: Tablet Manufacture, 1904, page 63.

Manufacturing Chemist, Feb. 1947, page 88.

Amer. J. Pharmacy, Sept. 1946, page 33 1.

Amer. J. Pharmacy, Oct. 1946, page 365.

J. Amer Pharm. Assoc. Scientific Edition, Nov. 1946, pages 326-7.

Science, Feb. 28, 1947, page 239.

The Lancet, March 29, 1947, pages 408-410.

Wood: Tablet Manufacture, (1904) pages 55 and 56.

Amer. J. Pharmacy, Sept. 1946, page 328. 

1. A COMMINUTED MIX SUITABLE FOR FORMING PENICILLIN-EPHEDRINE SALT TABLETS COMPRISING: A PENICILLIN SALT; A WATER-SOLUBLE EPHEDRINE SALT; BORIC ACID; A DRY ORGANIC ACID AND SODIUM BICARBONATE. 